Uterine tissue monitoring device and method

ABSTRACT

The invention provides a devices, methods and systems to measure and record uterine tissue environment components such as pH during the course of uterine artery occlusion. The uterus becomes ischemic due to the occlusion thereof, and its pH drops sharply within minutes of uterine artery occlusion and remains relatively low for a period of time. The return of normal pH is an indicator of return of blood to the ischemic tissue. In use, a catheter with a pH measuring tip is advanced through the patient&#39;s vaginal canal and into the patient&#39;s uterine cavity until the pH measuring active electrode on the distal end of the catheter contacts or penetrates the uterine fundus. The active electrode detects the pH and a signal representing pH is transmitted to a pH recording and monitoring device which preferably displays the pH. The signal may be transmitted through a conductor or by a radio transmitter. Components other than pH may be monitored such a pCO 2 , and pO 2 .

FIELD OF THE INVENTION

The invention relates generally to diagnostic measurements during thetreatment of uterine disorders by the reduction of blood flow through afemale patient's uterine artery.

BACKGROUND OF THE INVENTION

Hysterectomy (surgical removal of the uterus) is performed onapproximately 600,000 women annually in the United. States. Hysterectomyis often the therapeutic choice for the treatment of a variety ofuterine disorders such as cancer, adenomyosis, menorrhagia, uterineprolapse, dysfunctional uterine bleeding (abnormal menstrual bleedingthat has no discrete anatomic explanation such as a tumor or growth),and muscular tumors of the uterus, known as leimyoma or uterinefibroids.

However, hysterectomy is a drastic treatment, having many undesirablecharacteristics. Newer treatment methods have been developed for somediseases which avoid the need for a hysterectomy. For example, in 1995,it was demonstrated that uterine fibroids could be treated withouthysterectomy using a non-surgical therapy, specifically comprisingbilateral intraluminal occlusion of the uterine arteries (Ravina et al.,“Arterial Embolization to Treat Uterine Myomata”, Lancet Sep. 9, 1995;Vol. 346; pp. 671-672, incorporated in its entirety herein). Thistechnique is known as “uterine artery embolization”. In this technique,uterine arteries are accessed via a transvascular route from a commonfemoral artery into the left and right uterine arteries. The techniqueuses standard interventional radiology angiographic techniques andequipment, whereby the uterine arteries are accessed via a transvascularroute from a common femoral artery into the left and right uterinearteries. Uterine artery embolization can be effectively used to controluterine bleeding from a variety of sources using coils placed inarterial and venous lumens (See U.S. Pat. Nos. 4,994,069, 5,226,911, and5,549,824, all of which are incorporated in their entireties herein), orparticles (GELFOAM pledgets, available from Upjohn, Kalamazoo, Mich. orIVALON particles, available from Boston Scientific).

One of the key features for treating fibroids with uterine arteryembolization is the fact that fibroids live a tenuous vascular life withvery little ability to recruit a new blood supply from the host when theprimary blood supply is compromised. The uterus on the other hand has adual (or redundant) blood supply; the primary blood supply is from thebilateral uterine arteries, the secondary blood supply from thebilateral ovarian arteries. Consequently, when both uterine arteries areoccluded, i.e., bilateral vessel occlusion, the uterus and the fibroidscontained within the uterus are both deprived of their blood supply.However, as demonstrated by Ravina et al., the effect on the fibroids isgreater than the effect on the uterus. In most instances, the fibroidswither and cease to cause clinical symptoms.

The uterus has a dual (or redundant) blood supply, the primary bloodsupply being from the bilateral uterine arteries, and the secondaryblood supply from the bilateral ovarian arteries. Consequently, whenboth uterine arteries are occluded, i.e. bilateral vessel occlusion; theuterus and the fibroids contained within the uterus are both deprived oftheir blood supply. However, as demonstrated by Ravina et al., theeffect on the fibroid is greater than the effect on the uterus. In mostinstances, the fibroid withers and ceases to cause clinical symptoms.See also Burbank, et al., “Uterine Artery Occlusion by Embolization orSurgery for the Treatment of Fibroids: A Unifying Hypothesis-TransientUterine Ischemia,” The Journal of the American Association ofGynecologic Laparoscopists, November 2000, Vol. 7, No. 4 Supplement, pp.S3-S49. U.S. Pat. No. 6,254,601, to Burbank et al. entitled “Methods forOcclusion of the Uterine Arteries,” describes numerous devices andmethods useful for occluding a uterine artery.

The current treatments offered to women for fibroid treatment or uterinebleeding focus on permanent or near permanent occlusion methods for theuterine artery. For example, embolizing with PVA particles causesuterine artery occlusion for 6 months to permanent in situ); embolizingwith stainless steel coils causes permanent occlusion; embolizing withGelfoam occludes for 3 to 4 weeks before degradation of the embolicparticles; surgical ligation with metal vascular clips occludepermanently; and surgical ligation with RF ablation results in permanentocclusion.

The prior art devices and methods are therefore aimed at permanentocclusion of the uterine artery, resulting in redirection of the bloodflow to the uterus through collateral circulation. The patients whosuffer most dramatically from uterine myomata are women of child bearingage who may desire to bear additional children. The current methods ofembolizing or ligating uterine arteries are specifically contraindicatedfor women who desire to bear additional children. This is therealization of inadequate blood supply to the uterus because of the lossof the uterine arteries, the primary blood supply. While there have beenreports of women who have undergone uterine artery embolization with PVAparticles and who have subsequently become pregnant and deliver normalbabies. Women who have undergone uterine artery embolization have alsoexperienced premature menopause due to ovarian failure.

Recent advances in non-permanent occlusion of uterine arteries fortreating a variety of uterine disorders have relied upon time period todetermine when to re-establish blood flow through the patient's uterineartery. However, the duration of the uterine artery occlusion does notalways provide an accurate assessment of the treatment for a particulardisorder, particularly uterine fibroids.

SUMMARY OF THE INVENTION

The invention is directed to the detection of the extent of uterineartery occlusion in the treatment of uterine disorders in a femalepatient, and specifically, to monitoring of ionic components of thepatient's uterine tissue such as the endometrium and myometrium.

Occlusion of the uterine arteries alters the chemical environment ofuterine tissue in a time dependent fashion, typically in three phases,an initial phase, a dwell phase and a return phase. Before the occlusionof the uterine arteries, the pH of the uterine tissue can range fromabout 6.0 to about 7.5, usually about 6.3 to about 7.0. Upon theocclusion of the patient's uterine arteries, the pH of the tissue beginsto decline, the initial phase, as soon as it becomes ischemic which is afew minutes (typically about 2 to about 120 minutes, usually about 10 toabout 60 minutes). The pH of the uterine tissue declines in the initialphase about 0.2 to about 1.0. pH units, usually about 0.3 to about 0.7pH units. The pH stays at a lower level, the dwell phase, for about 10to about 120 minutes, typically about 10 to about 80 minutes. After thedwell phase, the pH returns to normal or near normal pH values thatexisted prior to the uterine artery occlusion which is the return phase.The initial phase can last about 10 to about 90 minutes, but typicallylast about 10 to about 60 minutes. The increase of the uterine tissue pHafter uterine artery occlusion is usually an indication that theischemic tissue is receiving blood flow from collateral arteries such asthe ovarian arteries, if the uterine arteries remain occluded. While thediscussion herein refers primarily directed to monitoring the pH ofuterine tissue, other species may be monitored such as pCO₂, and pO₂.Other components of the uterine tissue environment may be measured inthe same or similar fashion. With pH monitoring the initial phase is adescent phase and the return phase is an ascent phase. When othercomponents are monitored, the initial phase may be an ascent phase whilethe return phase is a descent phase.

The time for effective uterine artery occlusion treatments may vary frompatient to patient depending on a variety of factors, including theamount of collateral blood flow from the patient's ovarian and otherarteries. However, the short term pH changes in the patient's uterinetissue, which result from the uterine artery occlusion, provide a moreaccurate indication of the progress of the procedure than existingmethods.

These and other advantages of the invention will be evident from thefollowing detailed description of the invention hen taken in conjunctionwith the attached exemplary drawing.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic elevational view of the component monitoringsystem embodying features of the invention.

FIG. 2 is an enlarged elevational view of the monitoring systemillustrating the sheath and biasing mechanism for urging the operativeend of the monitor against the endometrium surface within the patient'suterine cavity.

FIG. 3 is a partial transverse cross-sectional view of the system shownin FIG. 2 taken along the lines 3-3.

FIG. 4 is a schematic illustration of a female patient's reproductiveorgans with a component monitor shown in FIG. 1 deployed within thepatient's uterine cavity.

FIG. 5 is a schematic view illustrating a monitoring electrode extendinginto a patient's myometrium.

FIG. 6 is a graph illustrating the pH changes to endometrial tissue andmyometrial tissue due to uterine artery occlusion over a period of time.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a component monitoring system 10 embodying featuresof the invention which includes a permeable distal antimony electrode11, an elongated shaft 12 having a proximal end 13 secured to a pHmonitoring unit 14 by a releasable connection 15. A reference externalelectrode 16, adapted to be secured to an exterior portion of thepatient, such as the patient's abdomen or thigh by suitable adhesive,has an elongated shaft 17 with a proximal end 18 secured to the pHmonitoring unit 14 by a releasable connection 19. The referenceelectrode is preferable a silver/silver chloride electrode. A suitablepH sensing electrode system is the Zinetics 24ME multi-use pH cathetersfrom Medtronic, Inc.

The pH monitoring unit 14 includes a personal digital assistant 20, suchas the Palm Pilot with a data acquisition system 21, such as a DataStickDAQ adapter. Shafts 12 and 17 are secured to the manifold 22 byreleasable connections 15 and 19 and transmission line 23 leads from themanifold 22 to a receiving port of the data acquisition system 21 totransmit the voltage differential between the active electrode 11 andthe reference electrode 16.

The pH monitoring system 10 includes an introducing sheath 24 which isconfigured to extend through the patient's vaginal canal and into theuterine cavity. The distal end 25 of sheath 24 is preferably providedwith a tapered non-traumatic tip. The proximal end 26 has a collar 27,an attached spring 28 and Toughy-Borst adapter 29 secured to theproximal end of the spring 28 and configured to be releasably secured tothe exterior of the shaft 12 of the active electrode 11.

FIGS. 2 and 3 illustrate in greater detail the introducer sheath 24. Thesheath 24 has an elongated shaft 32 with an inner lumen 33 configured toslidably receive the active electrode 11 and shaft 12 thereof, and adischarge port 34 at the distal end 25 of the sheath. The proximal endof the sheath has a pair of tabs or eyelets 35 for securing the proximalend to the patient, e.g. the patient's uterine cervix or vaginal labia,by a clip or suture or other suitable means.

As shown in FIG. 4, the active electrode 11 on the distal end of theshaft 12 is introduced into the patient's vaginal canal 34, advancedinto the uterine patient's uterine cavity 35 until the active electrode11 is pressed against the endometrial fundus 36 of the patient's uterus37 to monitor the pH of the endometrial tissue. After the sheath issecured to the patient, the Toughy-borst adapter 29 on the sheath 24 ispulled proximally to elongate the spring 28 and then tightened about theexterior of the shaft 12. The biasing action of the spring 28 urges theshaft 12 further into the patient's uterine cavity and presses theactive electrode 11 against the fundus 30 to ensure proper contact forpH detection of the endometrial lining of the patient's uterus 31.

An exterior reference electrode 16 is secured to the patient's skin at aconvenient place close to the patient's vaginal opening, e.g. theabdomen or thigh. The active electrode shaft 12 and the referenceelectrode shaft 17 are operatively connected to the manifold 22 of themonitor unit 14 at releasable connections 15 and 19 respectively. Theelectrical signals received from the active electrode 11 throughconductor 37 and reference electrode 16 through conductor 38 aretransmitted to the data acquisition system 21 through transmission line23. The endometrial tissue pH is displayed on the PDA.

As shown in FIG. 5, the active electrode 40 may be configured topenetrate the uterine wall through the endometrial layer 41 into themyometrial layer 42. The pH signals tend to be a little more stable.However, a coller 43 should be provided to limit the penetration intothe myometrial layer to prevent penetration through the uterine wall.

In some instances it may be desirable to provide an active electrodewith a radio transmitter which can be implanted into the uterine wallwithout a catheter extending out of the patient's vaginal canal. Amonitor is provided with a suitable receiver to receive the signal fromthe active electrode transmitter and display or record the receivedsignal as a function of the pH (or other component parameter). Thisallow for the use of a uterine artery clip or clips such as described inco-pending applications Ser. No. 01/113,096, filed on Mar. 28, 2002 andSer. No. 10/300,495, filed on Nov. 19, 2002, both of which have beenassigned to the present assignee Vascular Control Systems, Inc. Theclips may be applied to occlude the patient's uterine artery with the pHmonitor system installed to allow the patient sufficient mobility toleave the clinical setting without a catheter extending out o thepatient's vaginal canal and return when the pH monitor indicates thatthe uterine artery has been occluded long enough so that the uterineclip should be removed. The active electrode and transmitter may also beremoved.

The temporary occlusion of uterine arteries for the treatment foruterine fibroids and uterine bleeding from a variety of causes and themonitoring of the concentration of components, e.g. pH, in the uterinetissue environment can be effective. The procedure is illustrated in thefollowing example.

EXAMPLE

Ten women with menorrhagia, pelvic pain or pressure, and/or anemia hadmyomas and uteris larger than 13 weeks gestation were subjected tobilateral uterine artery occlusion. Prior to the uterine arteryocclusion a pH monitoring probe (Zinetics 24ME multi-use pH catheter)was placed transcervically into the endometrium and myometrium. Beforeuterine artery occlusion, the uterine tissue pH value for the 10patients averaged 6.7 pH units, ranging from 6.4 to 6.9. The averagedecline in pH during the initial phase was 0.5 pH units, ranging from0.4 to 0.6. The uterine tissue of all of the patients exhibited asimilar pattern of pH value changes over the monitoring period (lessthan 24 hours). The initial phase occurred over a period of about 5 toabout 150 minutes, averaging 32 minutes. The pH of uterine lining tissuedeclined an average of about 0.5 pH units during the initial phase. Inthe dwell phase, the pH levels of the uterine tissue remained atessentially the reduced levels over a period of about 5 to about 150minutes, averaging 53 minutes. In the return phase, the pH returned tothe pre-occlusion levels from the low pH levels of the dwell phase overa period of about 30 to about 180 minutes, averaging about 114 minutes.A typical display of the variation of pH of the endometrial andmyometrial tissue with respect to time due to the ischemic effects ofuterine artery occlusion is illustrated in FIG. 6.

While particular forms of the invention have been illustrated anddescribed herein, it will be apparent that various modifications andimprovements can be made to the invention. For example, while a porousantimony electrode was described as an active electrode a variety ofelectrodes may be used. Moreover, the reference electrode is describedherein as being attached to the exterior of the patient. However otherreference electrode locations may be employed. For example, the shaft ofthe monitoring system may have the active electrode and a referenceelectrode.

Individual features of embodiments of the invention may be shown in somedrawings and not in others, but those skilled in the art will recognizethat individual features of one embodiment of the invention can becombined with any or all the features of another embodiment.Accordingly, it is not intended that the invention be limited to thespecific embodiments illustrated. It is therefore intended that thisinvention to be defined by the scope of the appended claims as broadlyas the prior art will permit.

Terms such a “element”, “member”, “device”, “sections”, “portion”,“section”, “steps” and words of similar import when used herein shallnot be construed as invoking the provisions of 35 U.S.C. §112(6) unlessthe following claims expressly use the terms “means” or “step” followedby a particular function without specific structure or action. Allpatents and patent applications referred to above are herebyincorporated by reference in their entirety. Accordingly, it is notintended that the invention be limited, except as by the appendedclaims.

1. A method of monitoring the pH of tissue lining a female patient'suterine cavity during a medical treatment which includes occluding oneor more uterine arteries, comprising: a. providing a pH measuringcatheter having an elongated shaft with a proximal end, a distal end,and an active electrode on the distal end thereof for detecting a pHparameter; b. advancing the pH measuring catheter through the patient'svaginal canal until the distal end is located in the female patient'suterine cavity; c. urging the active electrode on the distal end of thepH measuring catheter into contact with uterine tissue within theuterine cavity; and d. generating a signal from the active electroderepresenting a pH parameter of the uterine tissue, wherein an introducersheath having an inner lumen is introduced through the patient's vaginalcanal into the patient's uterine cavity and is secured to the patientand the catheter is introduced through the inner lumen of the introducersheath.
 2. The method of claim 1 wherein a pH signal is generatedrepresenting the difference between the signal representing the pHparameter of the body cavity and a signal received from a referenceelectrode secured to an exterior portion of the patient.
 3. The methodof claim 2 wherein the difference signal is transmitted to a monitoringunit which displays pH units.
 4. The method of claim 1 wherein a biasingspring is secured between the introducer sheath and the pH measuringcatheter to urge the active electrode into contact with uterine tissue.5. The method of claim 4 wherein the uterine tissue is endometrialtissue.
 6. The method of claim 1 wherein the pH parameter of thepatient's uterine lining tissue is monitored by the active electrode forat least 0.5 hour.
 7. The method of claim 1 wherein the pH parameter ofthe patient's uterine lining tissue is monitored for a period of up toabout 48 hours.
 8. A method of treating a female patient's uterus,comprising: a. detecting the concentration of a component of uterinetissue environment; b. occluding one or more of the patient's uterinearteries; c. using a pH monitoring unit for monitoring the concentrationof the detected component after occluding one or more of the patient'suterine arteries; and d. re-establishing blood flow in the patient'suterine artery after the concentration of the detected component returnsto pre-occlusion levels or near pre-occlusion levels.
 9. The method ofclaim 8 wherein the detected component is the hydrogen ionconcentration.
 10. The method of claim 9 wherein the hydrogen ionconcentration is detected by a pH detecting electrode.
 11. The method ofclaim 8 wherein a pH measuring catheter having an elongated shaft with aproximal end and a distal end and an active electrode on the distal endthereof is advanced through the patient's vaginal canal, into the femalepatient's uterine cavity and the active electrode is urged into contactwith uterine tissue to detect a pH parameter.
 12. The method of claim 11wherein a signal is generated which represents the detected pHparameter.
 13. The method of claim 12 wherein a pH signal is generatedrepresenting the difference between the signal representing the pHparameter of the body cavity and a signal received from a referenceelectrode secured to the patient.
 14. The method of claim 11 wherein thedifference signal is transmitted to a monitoring unit which displays pHunits relating to the signal received.
 15. The method of claim 11wherein an introducer sheath with an inner lumen is introduced throughthe patient's vaginal canal into the patient's uterine cavity and issecured to the patient and the pH measuring catheter is introducedthrough the inner lumen of the introducer sheath into the patient'suterine cavity.
 16. The method of claim 15 wherein a biasing spring issecured between the introducer sheath and the pH measuring catheter tourge the active electrode into contact with uterine tissue.
 17. Themethod of claim 16 wherein the active electrode is urged into contactwith endometrial uterine tissue.
 18. The method of claim 16 wherein theactive electrode is urged into contact with myometrial uterine tissue.19. The method of claim 8 wherein the concentration of the detectedcomponent is monitored for at least 0.5 hour.
 20. The method of claim 8wherein the concentration of the detected component is monitored for aperiod of up to about 48 hours.